Sequence of therapy and survival in patients with advanced pancreatic neuroendocrine tumours.

Background: Pancreatic neuroendocrine tumours (pnets) often present as advanced disease. The optimal sequence of therapy is unknown. Methods: Sequential patients with advanced pnets referred to BC Cancer between 2000 and 2013 who received 1 or more treatment modalities were reviewed, and treatment patterns, progression-free survival (pfs), and overall survival (os) were characterized. Systemic treatments included chemotherapy, small-molecule therapy, and peptide receptor radionuclide therapy. Results: In 66 cases of advanced pnets, median patient age was 61.2 years (25%-75% interquartile range: 50.8-66.2 years), and men constituted 47% of the group. First-line therapies were surgery (36%), chemotherapy (33%), and somatostatin analogues (32%). Compared with first-line systemic therapy, surgery in the first line was associated with increased pfs and os (20.6 months vs. 6.3 months and 100.3 months vs. 30.5 months respectively, p < 0.05). In 42 patients (64%) who received more than 1 line of therapy, no difference in os or pfs between second-line therapies was observed. Conclusions: Our results confirm the primary role of surgery for advanced pnets. New systemic treatments will further increase options.

In the Era After the European Organisation for Research and Treatment of Cancer 'Boost' Study, is the Additional Radiotherapy to the Breast Tumour Bed Still Beneficial for Young Women?

AIMS: The European Organisation for Research and Treatment of Cancer (EORTC) 22,881-10,882 trial showed significant benefit of a radiotherapy boost (RTB) in women ≤40 years in a pre-hormone therapy (HT) era. We determined how the use of HT and RTB changed in response to clinical guidelines and whether the benefit of routine RTB was still observed in the HT era. MATERIALS AND METHODS: Between 1996 and 2004, a provincial database identified all women ≤40 years with breast cancer who met the inclusion criteria of the EORTC trial. In total, 411 patients were classified into three eras defined by the guidelines: era 1 (discretionary HT, discretionary RTB); era 2 (routine HT, discretionary RTB); era 3 (routine HT, routine RTB). HT use, RTB use and cumulative incidence of local recurrence were calculated and compared across eras. RESULTS: HT use increased after the first policy change from 13% to 75% for oestrogen receptor-positive patients (P < 0.01). RTB use also increased from 33% to 76% following the second policy change (P < 0.01). At 10 years, the cumulative incidence of local recurrence was 12% in era 1, 6% in era 2 and 6% in era 3 (era 2 versus era 3, P = 0.92). For patients in the routine HT era (eras 2 and 3 combined) there was no significant difference in local recurrence between RTB and 'no RTB' patients (6% versus 7%, P = 0.81). CONCLUSIONS: The routine use of HT and RTB increased significantly after new practice guidelines. Introduction of the HT guideline was associated with a 6% improvement in local recurrence at 10 years. No improvement in local recurrence was associated with the introduction of the RTB guideline in the HT era. The routine use of a boost in unselected young women with negative margins should be re-evaluated in the current HT era.

Impact of pathologic complete response on survival after neoadjuvant chemotherapy in early-stage breast cancer: a population-based analysis.

BACKGROUND: Achieving a pathologic complete response (pCR) has been associated with improved long-term outcomes in clinical trials. However, the benefit of achieving pCR across subtypes and its prognostic effect on real-world outcomes has not been well described. METHODS: A retrospective analysis of the Breast Cancer Outcomes Unit database was undertaken to identify patients with stage I-III breast cancer treated with neoadjuvant chemotherapy from 2005 to 2010 in British Columbia. Patients were separated into two groups: those with pCR and those with residual invasive disease in the breast/axillary lymph nodes (RD). The primary endpoint was relapse-free survival (RFS). Key secondary endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). RESULTS: Of 267 patients identified, 74 patients (28%) achieved pCR and 193 patients (72%) had RD. Median follow-up was 7.5 years. The 5-year RFS was higher in the pCR group compared to the RD group (84% vs 70%; HR 0.45, p = 0.011). The 5-year BCSS was also higher in the pCR group than in the RD group (90% vs 77%; HR 0.39, p = 0.014). In multivariable analyses, pCR was associated with improved RFS (HR 0.39, p = 0.0077) and BCSS (HR 0.35, p = 0.015), whereas traditional pathological prognostic factors were not. Patients with TNBC who achieved pCR had improved RFS and BCSS compared to those with RD (HR 0.26, p = 0.020 and HR 0.35, p = 0.090, respectively). A similar but non-statistically significant trend was seen in the HER-2-positive and ER + subtypes. CONCLUSIONS: Achieving pCR after neoadjuvant chemotherapy was associated with clinically meaningful improvements in survival parameters in a real-world setting. The cumulative data support pCR as a valid surrogate endpoint in both clinical trials and population-based settings.

Prescribing practices of endocrine therapy for ductal carcinoma in situ in British Columbia.

Purpose: The mainstay of treatment for ductal carcinoma in situ (dcis) involves surgery in the form of mastectomy or lumpectomy. Inconsistency in the use of endocrine therapy (et) for dcis is evident worldwide. We sought to assess the variation in et prescribing for patients with dcis across a population-based radiotherapy (rt) program and to identify variables that predict its use. Methods: Data from a breast cancer database were obtained for women diagnosed with dcis in British Columbia from 2009 to 2014. Associations between et use and patient characteristics were assessed by chi-square test and multilevel multivariate logistic regression. The Kaplan-Meier method, with propensity score matching and Cox regression analysis, was used to assess the effects of et on overall survival (os) and relapse-free survival (rfs). Results: For the 2336 dcis patients included in the study, et use was 13% in dcis patients overall, and 17% in patients with estrogen receptor-positive (er+) tumours treated with breast-conserving surgery and rt. Significant variation in et use by treatment centre was observed (range: 8%-23%; p < 0.001), and prescription of et by individual oncologists varied in the range 0%-40%. After controlling for confounding factors, age less than 50 years [odds ratio (or): 1.72; p = 0.01], treatment centre, er+ status (or: 5.33; p < 0.001), and rt use (or: 1.77; p < 0.001) were significant predictors of et use. No difference in os or rfs with the use of et was observed. Conclusions: In this population-based analysis, 13% of patients with dcis in British Columbia received et, with variation by treatment centre (8%-23%) and individual oncologist (0%-40%). Age less than 50 years, er+ status, and rt use were most associated with et use.

Factors affecting radiotherapy prescribing patterns in the post-mastectomy setting.

Background: Radiation therapy (rt) after mastectomy for breast cancer can improve survival outcomes, but has been associated with inferior cosmesis after breast reconstruction. In the literature, rt dose and fractionation schedules are inconsistently reported. We sought to determine the pattern of rt prescribing practices in a provincial rt program for patients treated with mastectomy and reconstruction. Methods: Women diagnosed with stages 0-iii breast cancer between January 2012 and December 2013 and treated with curative-intent rt were identified from a clinicopathology database. Patient demographic, tumour, and treatment information were extracted. Of the identified patients, those undergoing mastectomy were the focus of the present analysis. Results: Of 4016 patients identified, 1143 (28%) underwent mastectomy. The patients treated with mastectomy had a median age of 57 years, and 37% of them underwent reconstruction. Treatment with more than 16 fractions of rt was associated with autologous reconstruction [odds ratio (or): 37.2; 95% confidence interval (ci): 11.2 to 123.7; p < 0.001], implant reconstruction (or: 93.3; 95% ci: 45.3 to 192.2; p < 0.001), and treating centre. Hypofractionated treatment was associated with older age (or: 0.94; 95% ci: 0.92 to 0.96; p < 0.001), and living more than 400 km from a treatment centre (or: 0.37; 95% ci: 0.16 to 0.86; p = 0.02). Conclusions: Prescribing practices in breast cancer patients undergoing mastectomy are influenced by reconstruction intent, age, nodal status, and distance from the treatment centre. Those factors should be considered when making treatment decisions.

Prognostic effect of sidedness in early stage versus advanced colon cancer.

BACKGROUND AND AIMS: The prognostic effect of sidedness in colorectal cancer has been evaluated in numerous prospective and retrospective cohorts. Most of these have reported overall survival data; there is scant relapse-free survival data in early stage disease. This study aimed to determine the effect of tumor sidedness in survival in early stage and relapsed colon cancer. METHODS: Patients with stage I-III colorectal cancer were identified from the BC Cancer Agency Gastrointestinal Cancer Outcomes Unit. Survival analysis by stage and sidedness was compared with the log-rank test. Baseline characteristics were controlled by multivariate Cox-proportional hazard models. In relapsed patients, bevacizumab and EGFR inhibitor (EGFRI) treatments were included and tested for interaction. RESULTS: Among 5378 patients with stage I-III colon cancer, patients with right-sided stage II tumors experienced better relapse-free survival compared with those with left-sided tumors; right-sidedness was not prognostic for RFS in stage III disease. When survival was considered in patients who relapsed, right-sided tumors had inferior survival after relapse in both stage II and stage III tumors. At relapse, right-sided outcomes were inferior regardless of biologic therapy. An interaction test revealed a significant association between sidedness and survival with EGFRIs. CONCLUSIONS: In this large, population-based study, right-sided presentation has a significant prognostic impact: in early stage, right-sidedness is favorably prognostic among stage II tumors and not prognostic in stage III disease. After relapse, right- sidedness is associated with an inferior prognosis, regardless of initial stage of presentation. Colon tumor sidedness is independently prognostic and may be considered in treatment assignment for both early stage and advanced disease.

Neoadjuvant systemic therapy in breast cancer: use and trends in radiotherapy practice.

BACKGROUND: The use of neoadjuvant systemic therapy (nast) in the treatment of breast cancer is increasing, and the role of adjuvant radiation therapy (rt) in that setting is uncertain. We sought to review and report the use of nast, its trends over time, and its relationship with the prescribing patterns of locoregional rt in a provincial cancer system. METHODS: Patients with stages i-iii breast cancer diagnosed during 2007-2012 were identified using a provincial database. Patient, tumour, and treatment characteristics were extracted. Multivariable logistic regression analyses were used to assess associations with the use of nast. Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Of the 11,658 patients who met the inclusion criteria, 602 (5%) had received nast. Use of nast was more frequent in stage iii patients (53%) than in stages i and ii patients (2%). In clinically lymph-node positive patients, a pathology assessment was made approximately 50% of the time. Higher clinical tumour stage and increasing clinical nodal stage predicted for increasing use of nast and of nodal rt after nast, but pathologic nodal status after nast was not associated with use of nodal rt. A statistically significant survival difference was observed between patients in the nast and no-nast groups, but that significance disappeared in a multivariable Cox regression analysis. CONCLUSIONS: This population-based study demonstrated 5% use of nast for breast cancer. Most patients received nodal rt after nast, and nodal rt was not associated with pathologic stage after nast. Findings likely reflect the realities of clinical practice and show that reliance on clinical nodal staging results in outcomes similar to those reported in the literature.

The heart of the matter: cardiac assessment in professional footballers.

AIM: Sudden cardiac death is the leading medical cause of death during exercise.1 Our objective was to retrospectively analyse the routine cardiac assessment of professional footballers to aid physician management and improve player safety. METHODS: Footballers from five professional clubs between March 2012 and October 2014 were included (n=265). All were performed in line with the recommendations of the Football Association Cardiology Committee, incorporating clinical examination, 12-lead ECG, echocardiography and health questionnaire.2 Data was retrospectively collected, inspected and analysed using Excel spreadsheets. Findings were classified as 'normal' or 'not normal', and not normal assessments were further broken down into 'clear-cut pathology' (pathology with widely accepted guidance on management) or 'grey screen'. RESULTS: Footballers were aged 13 to 37 years, with 69% aged over 18 and 31% under. The majority of the review population was White European (66%). Of the review population 11% had 'not normal' assessments, of these assessments 83% were considered grey screens (by Consultant Cardiologist) requiring further investigation or surveillance. Overall clear-cut pathology was identified in 2%. CONCLUSIONS: A high proportion of the players (9%) had grey screens. The majority of these were due to ECG or structural abnormalities, which are clinically challenging to differentiate from physiological adaptation of the athletic heart and potentially fatal conditions. The extent to which these findings put the athlete at risk of a life threatening cardiac event is un-?quantified. Team physician's need to be aware of managing the on-going risk with these patients and ensure suitable ?follow up and assessment on a regular basis to mitigate this.

Patterns of practice with third-line anti-EGFR antibody for metastatic colorectal cancer.

BACKGROUND: Therapy with anti-epidermal growth factor receptor (egfr) monoclonal antibody improves outcomes for patients with metastatic colorectal cancer (mcrc) in the first-, second-, and third-line trial settings. In British Columbia, the use of egfr inhibitors (egfris) is confined to third-line therapy, which might lower the proportion of patients who receive this therapy. The objective of the present study was to describe egfri treatment patterns when those agents are limited to the third-line setting. The results will inform decisions about optimal use of egfri agents, including earlier in the course of therapy for metastatic disease. METHODS: All patients with newly diagnosed mcrc who were referred to BC Cancer Agency clinics in 2009 were included in the study. Prognostic and treatment information was prospectively collected; KRAS test results were determined by chart review. RESULTS: The study included 443 patients with a median age of 66 years. For the 321 patients who received systemic therapy, median survival was 22.3 months. Of the 117 patients who were treated with 5-fluorouracil, oxaliplatin, and irinotecan, and who were potentially eligible for egfri therapy, 90% (105 patients) were tested for KRAS status. Of the 60 patients with KRAS wild-type tumours, 82% (49 patients) received egfri therapy. CONCLUSIONS: When egfri therapy is limited to the third-line setting, only a small proportion of patients receive such therapy, with death and poor performance status preventing its use in the rest. Availability of egfri in earlier lines of therapy could increase the proportion of patients treated with all active systemic agents.

Population-based analysis of the impact and generalizability of the NSABP-B24 study on endocrine therapy for patients with ductal carcinoma in situ of the breast.

BACKGROUND: In 1999, the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B24 trial demonstrated that tamoxifen reduced relapse risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and radiotherapy (RT). In 2002, Allred's subgroup analysis showed that tamoxifen mainly benefitted estrogen receptor (ER)-positive disease. This study evaluates the impact and generalizability of these trial findings at the population level. PATIENTS AND METHODS: From 1989 to 2009, 2061 women with DCIS underwent BCS + RT in British Columbia. The following cohorts were analyzed: (1) pre-NSABP-B24 era (1989-1998, N = 417); (2) post-NSABP-B24 era (2000-2009, N = 1548). Cohort 2 was further divided into pre- and post-Allred eras. RESULTS: Endocrine therapy (ET) was used in 404/2061 (20%) patients. Median age of patients treated with compared with without ET, was 53 versus 57 years, (P < 0.0005). One of 417 (0.2%) versus 399/1548 (26%) patients took ET before versus after NSABP-B24. Among the post-Allred era cohort treated with ET (N = 227), tumors were ER-positive in 65%, ER-negative in 1%, and ER-unknown in 33%; whereas of those treated without ET (N = 801), ER was positive in 43%, negative in 15%, and unknown in 42% (P < 0.0005). On multivariable analysis of the post-NSABP-B24 era, ET was associated with improved event-free survival (EFS) (hazard ratio 0.6; P = 0.02); 5-year EFS were 96.9% with ET versus 94.5% without ET. CONCLUSIONS: ET use in DCIS patients treated with BCS + RT increased significantly after the NSABP-B24 study. ER+ disease and younger age were associated with increased ET use. ET was associated with improved EFS, confirming the generalizability of trial data at a population level.

High-throughput transcriptomic analysis nominates proteasomal genes as age-specific biomarkers and therapeutic targets in prostate cancer.

BACKGROUND: Although prostate cancer (PCa) is hypothesized to differ in nature between younger versus older patients, the underlying molecular distinctions are poorly understood. We hypothesized that high-throughput transcriptomic analysis would elucidate biological differences in PCas arising in younger versus older men, and would nominate potential age-specific biomarkers and therapeutic targets. METHODS: The high-density Affymetrix GeneChip platform, encompassing >1 million genomic loci, was utilized to assess gene expression in 1090 radical prostatectomy samples from patients with long-term follow-up. We identified genes associated with metastatic progression by 10 years post-treatment in younger (age<65) versus older (age⩾65) patients, and ranked these genes by their prognostic value. We performed Gene Set Enrichment Analysis (GSEA) to nominate biological concepts that demonstrated age-specific effects, and validated a target by treating with a clinically available drug in three PCa cell lines derived from younger men. RESULTS: Over 80% of the top 1000 prognostic genes in younger and older men were specific to that age group. GSEA nominated the proteasome pathway as the most differentially prognostic in younger versus older patients. High expression of proteasomal genes conferred worse prognosis in younger but not older men on univariate and multivariate analysis. Bortezomib, a Food and Drug Administration approved proteasome inhibitor, decreased proliferation in three PCa cell lines derived from younger patients. CONCLUSIONS: Our data show significant global differences in prognostic genes between older versus younger men. We nominate proteasomeal gene expression as an age-specific biomarker and potential therapeutic target specifically in younger men. Limitations of our study include clinical differences between cohorts, and increased comorbidities and lower survival in older patients. These intriguing findings suggest that current models of PCa biology do not adequately represent genetic heterogeneity of PCa related to age, and future clinical trials would benefit from stratification based on age.

Panitumumab monotherapy compared with cetuximab and irinotecan combination therapy in patients with previously treated KRAS wild-type metastatic colorectal cancer.

BACKGROUND: The survival benefit for single-agent anti-epidermal growth factor receptor (egfr) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan. METHODS: The study enrolled patients with KRAS wt mcrc previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab-irinotecan before April 1, 2011, at the BC Cancer Agency (bcca). Patients were excluded if they had received anti-egfr agents in earlier lines of therapy. Data were prospectively collected, except for performance status (ps), which was determined by chart review. Information about systemic therapy was extracted from the bcca Pharmacy Database. RESULTS: Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab-irinotecan. Compared with patients treated with cetuximab-irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ecog) ps of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab-irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ecog ps of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01). CONCLUSIONS: Single-agent panitumumab and cetuximab-irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mcrc.

Evaluation of the clinical benefits of nanoparticle albumin-bound paclitaxel in women with metastatic breast cancer in British Columbia.

BACKGROUND: Altered formulations of taxanes may lack cross-resistance with standardly used solvent-based taxanes. The primary objective of the present study was to assess the clinical benefit of nanoparticle albumin-bound (nab)-paclitaxel in women with metastatic breast cancer previously treated with and without adjuvant taxane in British Columbia. METHODS: The BC Cancer Agency Pharmacy data repository and Breast Cancer Outcomes Unit database were linked to identify all patients who received nab-paclitaxel in British Columbia since its introduction in 2007. Hormone receptor status, demographic characteristics, number of cycles prescribed, and time to treatment failure were extracted and analyzed. RESULTS: From 2007 to 2011, 138 patients in British Columbia received nab-paclitaxel, with 122 patients available for analysis. Most (70.5%) received adjuvant chemotherapy; about a quarter (24.6%) received an adjuvant taxane. Patients who received adjuvant taxane were more likely to have node-positive (86.7% vs. 48.9%, p = 0.007), estrogen receptor-negative (46.7% vs. 13.0% p < 0.001) disease and to receive initial adjuvant radiotherapy (76.7% vs. 51.1%, p < 0.001). For the entire cohort, the median number of nab-paclitaxel cycles prescribed was 4.4 (range: 0.3-13). The median number of nab-paclitaxel cycles was greater when that agent was given as first- or second-line therapy than as third-line or greater therapy (5.0 cycles vs. 3.7 cycles respectively). The median time to treatment failure was 96 days in the prior adjuvant taxane group (range: 0-361) and 73.5 days in the no prior adjuvant taxane group (range: 0-1176). CONCLUSIONS: This retrospective study demonstrates potential clinical activity of nab-paclitaxel in metastatic breast cancer regardless of whether patients had prior exposure to adjuvant taxanes.

A Survey of Phytophthora spp. in Midwest Nurseries, Greenhouses, and Landscapes.

A survey of nurseries, greenhouses, and landscapes was conducted from 2006 to 2008 in order to determine the prevalence and diversity of Phytophthora spp. From sites in Iowa, Michigan, Ohio, and, predominantly, Indiana, 121 Phytophthora isolates were obtained from 1,657 host samples spanning 32 host genera. Based on sequence of the internal transcribed spacer (ITS) region of the ribosomal DNA, 11 Phytophthora spp. and two hybrid species were identified. A majority of the isolates were P. citricola (35.9%) or P. citrophthora (27.4%). Six isolates were confirmed as hybrids (four of P. cactorum × hedraiandra and two of P. nicotianae × cactorum) by cloning and sequencing the ITS region. Three P. cactorum × hedraiandra isolates were obtained from the same site, from three Rhododendron spp., which are known hosts to the parental species. The fourth isolate, however, was recovered out of a different location in a Dicentra sp., which is not a known host to either parental species, suggesting an expansion of host range of the hybrid isolate as compared with either parental species.

Outcomes of women with early-stage breast cancer receiving adjuvant trastuzumab.

INTRODUCTION: Large randomized trials assessing the benefit of adjuvant trastuzumab in early-stage breast cancer positive for the human epidermal growth factor receptor 2 (her2) have demonstrated a significant improvement in survival. The objective of the present study was to describe the outcomes of women who received adjuvant trastuzumab for her2-positive breast cancer in British Columbia since publicly funded population-based use was initiated in July 2005. METHODS: Women from British Columbia, newly diagnosed with stage i-iii breast cancer between July 2004 and December 2006, who were positive for her2 overexpression by immunohistochemistry (3+) or amplification by fluorescence in situ hybridization (ratio ≥ 2.0) were included in the study. Data were collected from the prospectively assembled BC Cancer Agency Outcomes Unit, with cases linked to the provincial pharmacy data repository to determine the proportion of women who received adjuvant trastuzumab. RESULTS: Our retrospective study identified 703 her2-positive patients, of whom 480 (68%) received trastuzumab. In patients receiving trastuzumab, the 2-year relapse-free survival was 96.1% [95% confidence interval (CI): 93.6% to 97.7%] and the overall survival was 99.3% (95% CI: 97.9% to 99.8%). Among node-negative and -positive patients, the 2-year relapse-free survival was 97.8% and 94.8% respectively (p = 0.09) for the trastuzumab-treated group and 90.9% and 77.3% (p = 0.01) for the group not receiving trastuzumab (n = 223). Site of first distant metastasis was the central nervous system in 19.5% of the entire cohort and in 37.5% of patients treated with trastuzumab. DISCUSSION: This population-based analysis of adjuvant trastuzumab use among Canadian women demonstrates highly favorable outcomes at the 2-year follow-up.

A comparison of surgical and radiotherapy breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of "optimal" therapy.

BACKGROUND: Different jurisdictions report different breast cancer treatment rates. Evidence-based utilization models may be specific to derived populations. We compared predicted optimal with actual radiotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN: Data were analyzed for differences in demography, tumor, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual surgery/radiotherapy rates from 2 population-based and 1 institution-based registries were compared for patients diagnosed with breast cancer between 2000 and 2004, and 2002 for British Columbia. RESULTS: Mastectomy rates differed between British Columbia (40%), Western Australia (44%), and Dundee (47%, p<0.01). Radiotherapy rates differed between British Columbia (60%), Western Australia (52%), and Dundee (49%, p<0.01). Actual radiotherapy utilization rates were lower than optimal estimates. Region-specific optimal utilization rates at diagnosis varied from 57% to 71% for radiotherapy and 62% to 64% when taking into account patient preference. Variation was attributed to local differences in demography and tumor stage. CONCLUSIONS: Actual treatment rates varied, and were associated with patterns of care and guideline differences. Actual radiotherapy rates were lower than optimal rates. Differences between optimal and actual utilization may be due to access shortfalls, and patient preference.

Is breast-conserving therapy a safe option for patients with tumor multicentricity and multifocality?

BACKGROUND: We compared outcomes after breast-conserving therapy (BCT) and mastectomy in multicentric (MC)/multifocal (MF) versus unifocal breast cancer. PATIENTS AND METHODS: Women with stage I-II disease were classified as having unifocal or MC/MF disease. MC/MF and other prognostic factors were compared using binary logistic regression analysis. Univariate and multivariate analyses (MVAs) for relapse were carried out using cumulative incidence curves and Fine and Gray regression models. For the BCT group, matched analysis was added. RESULTS: Median follow-up was 7.9 years, 11 983 having BCT (unifocal: 11 683, MC/MF: 300) and 7771 having mastectomy (unifocal: 6884, MC/MF: 887). MC/MF patients treated with BCT were 50-69 years old, free of extensive ductal carcinoma in situ (DCIS), and had smaller tumors. The cumulative 10-year local recurrence rates among unifocal and MC/MF disease were 4.6% [95% confidence interval (CI) 4.1% to 5.0%] versus 5.5% (95% CI 2.6% to 9.9%) for the BCT group, P = 0.76 and 5.8% (95% CI 5.2% to 6.5%) versus 6.5% (95% CI 4.7% to 8.7%) for the mastectomy group, P = 0.77. MC/MF was not a significant factor for relapse or survival on MVA. In the matched analysis, relapse rates were similar in the unifocal and MC/MF groups, P = 0.60. CONCLUSION: BCT is a reasonable option in selected MC/MF cases, particularly those women aged 50-69 years old with small (<1 cm) MF tumors and without an extensive DCIS component.

Tumor markers in metastatic breast cancer subtypes: frequency of elevation and correlation with outcome.

BACKGROUND: Little is known about the correlations between tumor markers (TMs), breast cancer subtypes, site(s) of metastasis and prognosis. METHODS: Women diagnosed with metastatic breast cancer were included. Breast cancer subtypes were defined as LuminalA, LuminalB, LuminalHer2, Her2, Basal and non-Basal triple negative (TN). Levels of elevation of TM values [cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA 125)] among the subtypes were analyzed. Site(s) of metastasis and outcomes were captured. RESULTS: Eight hundred and ten patients were included. Luminal subtypes were associated with an elevation in at least one TM: 90.8% of LuminalHer2+, 90% of LuminalB and 88.6% of LuminalA. TMs were less frequently elevated in Basal (74.1%) and non-Basal TN (71.4%) cases (P < 0.001). CA 15-3 was the most frequently elevated TM. The incidence of TM elevation did not differ between patients with solitary versus multiple metastatic sites. Breast cancer-specific survival (BCSS) was significantly worse for patients with elevated TMs (P = 0.001). CONCLUSIONS: TM elevation of CA 15-3, CEA and/or CA 125 was documented in the majority of patients with metastatic breast cancer with CA 15-3 occurring most commonly. Luminal subtypes expressed elevated TMs significantly more frequently compared with the non-Luminal groups. TM elevation was not different between the different sites of metastasis. Overall, elevated TMs predicted a worse BCSS.

Does HER2 status influence locoregional failure rates in breast cancer patients treated with mastectomy for pT1-2pN0 disease?

BACKGROUND: The impact of HER2 overexpression on the locoregional control of breast cancer is controversial. PATIENTS AND METHODS: Data on 906 women diagnosed with pT(1-2)pN(0) breast cancer from 1986 to 1992 with known HER2 status and treated with a modified radical mastectomy without adjuvant radiotherapy or adjuvant trastuzumab were analyzed with respect to local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant relapse-free survival (DRFS). Log-rank statistics were used to compare 10-year Kaplan-Meier curves of LRFS, RRFS and DRFS in HER2+ and HER2- patients. RESULTS: Median follow-up was 12.8 years. HER2+ patients had a worse DRFS (P = 0.028) but there was no statistically significant difference in LRFS or RRFS between HER2+ and HER2- patients (P = 0.32 and 0.24 for LRFS and RRFS, respectively). Ten-year LRFS estimates among HER2+ patients was 91.3% and 86.9% for HER2- patients. Ten-year RRFS estimates for HER2+ and HER2- patients were 88.0% and 93.0%, respectively. CONCLUSION: HER2 overexpression was not associated with higher local or regional recurrence risk in subjects with pT(1-2)pN(0) breast cancer following mastectomy and nodal dissection after a median follow-up of >12 years.